The objective of this proposal is to investigate and to elucidate the physiologic role of 16 alpha-hydroxylated steroids focusing on 16 alpha-hydroxyprogesterone. Recent clinical studies utilizing a sensitive and specific radioimmunoassay reveal significant changes in blood concentrations of this steroid in humans during the menstrual cycle, pregnancy and after stimulation and supression of the pituitary-adrenal axis. Clinical studies will evaluate the temporal relationship of changes in the blood levels of this steroid to other hormonal parameters during pregnancy and the menstrual cycle in volunteers. The marked elevations of maternal blood concentrations of this steroid in the third trimester of pregnancy are attributed to the feto-placental unit. The significance of fetal elaboration of 16 alpha-hydroxyprogesterone during intrauterine development is presently unknown. Determination of maternal blood levels of this steroid in women with medical complications during pregnancy may be a reliable assessment of fetal distress. In addition to studies in humans, investigations of the significance of 16 alpha-hydroxyprogesterone in menstrual regulation and ovarian hormone secretions will be performed in Rhesus monkeys using in vivo and in vitro methods. From recent experiments on this species it is evident that this steroid is secreted by the ovaries in vivo and that intact follicles release 16 alpha-hydroxyprogesterone in tissue culture.